rs34772283

Variant names:

• chr1-64142520-C-T
• rs34772283
• NM_005012.4:c.1044C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005012.4(ROR1):​c.1044C>T​(p.Thr348Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,614,128 control chromosomes in the GnomAD database, including 486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (241 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (245 hom.)
• Consequence: ROR1 NM_005012.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.79
• Publications: 3 publications found

Genes affected

ROR1 (HGNC:10256): (receptor tyrosine kinase like orphan receptor 1) This gene encodes a receptor tyrosine kinase-like orphan receptor that modulates neurite growth in the central nervous system. The encoded protein is a glycosylated type I membrane protein that belongs to the ROR subfamily of cell surface receptors. It is a pseudokinase that lacks catalytic activity and may interact with the non-canonical Wnt signalling pathway. This gene is highly expressed during early embryonic development but expressed at very low levels in adult tissues. Increased expression of this gene is associated with B-cell chronic lymphocytic leukaemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2012]

ROR1-AS1 (HGNC:40508): (ROR1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-64142520-C-T is Benign according to our data. Variant chr1-64142520-C-T is described in ClinVar as Benign. ClinVar VariationId is 586409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR1	NM_005012.4	MANE Select	c.1044C>T	p.Thr348Thr	synonymous	Exon 7 of 9	NP_005003.2	Q01973-1
	ROR1	NM_001083592.2		c.1044C>T	p.Thr348Thr	synonymous	Exon 7 of 7	NP_001077061.1	Q01973-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROR1	ENST00000371079.6	TSL:1 MANE Select	c.1044C>T	p.Thr348Thr	synonymous	Exon 7 of 9	ENSP00000360120.1	Q01973-1
	ROR1	ENST00000371080.5	TSL:1	c.1044C>T	p.Thr348Thr	synonymous	Exon 7 of 7	ENSP00000360121.1	Q01973-3
	ROR1-AS1	ENST00000424995.2	TSL:2	n.89+28689G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4614 AN: 152130 Hom.: 241 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.00777 AC: 1952 AN: 251332 AF XY: 0.00557

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00313 AC: 4570 AN: 1461880 Hom.: 245 Cov.: 31 AF XY: 0.00268 AC XY: 1948 AN XY: 727240

African (AFR) AF: 0.112 AC: 3742 AN: 33480

American (AMR) AF: 0.00483 AC: 216 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.0101 AC: 58 AN: 5766

European-Non Finnish (NFE) AF: 0.000108 AC: 120 AN: 1112002

Other (OTH) AF: 0.00664 AC: 401 AN: 60396

GnomAD4 genome AF: 0.0305 AC: 4637 AN: 152248 Hom.: 241 Cov.: 32 AF XY: 0.0293 AC XY: 2179 AN XY: 74436

African (AFR) AF: 0.106 AC: 4392 AN: 41534

American (AMR) AF: 0.0111 AC: 169 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68018

Other (OTH) AF: 0.0237 AC: 50 AN: 2110

Alfa AF: 0.0131 Hom.: 58

Bravo AF: 0.0347

Asia WGS AF: 0.00722 AC: 26 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.039
DANN	Benign	0.82
PhyloP100		-2.8
Mutation Taster		=285/15	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34772283; hg19: chr1-64608203;